282 Neurology India | May-Jun 2009 | Vol 57 | Issue 3

Address for correspondence: Dr. Arun George Department of Neurology, Medical College, Calicut - 673 008, Kerala, India. E-mail: a.george@rediffmail.com

DOI: 10.4103/0028-3886.53276

Introduction

Guillain Barr syndrome (GBS) affects between one and four per 100,000 of the population annually throughout the world[1] causing respiratory failure requiring ventilation in approximately 25%, death in 4-15%[2-4],persistent disability in approximately 20%[5] and persistent fatigue in 67%.[6] GBS has been classified on a pathologic basis into demyelinating and axonal forms. Axonal GBS has been classified further into two groups: Acute motor axonal neuropathy (AMAN) and acute motor and sensory axonal neuropathy (AMSAN).[7] The principal clinical method for distinguishing AMAN, AMSAN, and acute inflammatory demyelinating polyneuropathy (AIDP) is electrodiagnostic, and clear criteria have been formulated. The pathology of AMAN and AMSAN is very similar, and both conditions may follow Campylobacter jejuni enteritis. The clinical picture

AbstractBackground: Guillain-Barr syndrome (GBS) is an acute neurological illness affecting the peripheral nervous system causing significant morbidity. The syndrome has been classified electrophysiologically into demyelinating and axonal forms. The clinical features of the axonal variant (acute motor axonal neuropathyAMAN) are not well characterized, particularly in the Indian context. Objective: To assess the incidence, clinical presentation and disease course of patients with AMAN. Materials and Methods: This is an observational study done at a tertiary referral center in South India. The study period extended from January 2006 to July 2007. All patients with a clinical diagnosis of GBS and satisfying the electrophysiological criteria for AMAN were included. Results: There were 12 cases of AMAN out of a total of 84 cases of GBS. All AMAN patients showed a characteristic pattern of hand weakness predominant weakness of finger extensors with relatively normal power in finger flexors, wrist flexors and extensors. Proximal limb weakness was mild and was present in 85% cases. One patient had cranial nerve palsy and one had hyperreflexia. None of the patients progressed to respiratory failure. Conclusion: AMAN is a distinct subgroup in GBS showing certain distinguishing features, the most notable being predominant weakness of finger extensors.

Key words: AMAn, finger drop, Guillain-Barr syndrome, hypereflexia, paucity of cranial nerve palsy

Finger drop sign in Guillain-Barr syndrome

Arun George, P. Abdurehiman, Jose James

Department of Neurology, Medical College, Calicut - 673 008, Kerala, India

Original Article

of AMAN has not been well characterized, particularly in the Indian context. Here we report 12 consecutive cases of AMAN which showed a characteristic pattern of predominant finger extensor weakness.

Materials and Methods

This is an observational study conducted in a tertiary referral center in south India. The study period extended from January 2006 to July 2007. The purpose of the study was to assess the incidence, clinical presentation and the disease course of patients with AMAN. All patients with a clinical diagnosis of GBS and electrophysiological criteria satisfying AMAN were included. Electrophysiological studies were performed within 10 days of the onset of illness in all patients. Nerve conduction studies were performed by the conventional procedures. Motor conduction studies were done on the median, ulnar,

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tibial, and peroneal nerves and sensory conduction studies on the median, ulnar, and sural nerves on both sides. (This is the standard protocol of nerve conduction study followed in our institution for GBS irrespective of AMAN or AIDP.) Patients were classified as having AMAN or AIDP based on the electrodiagnostic criteria proposed by Hughes and Cornblath recently; i.e. none of the features of AIDP except one demyelinating feature allowed in one nerve if distal compound muscle action potential (CMAP) was less than 10% of lower limit of normal and sensory action potential amplitudes were normal.[8] Blood cell counts and routine blood chemistry tests were done at the first neurological examination. CSF analysis was done before treatment in all patients.

A patient was excluded in the presence of at least one of the following: (1) marked, persistent asymmetry of the neurological signs (asymmetry was considered to exist when the MRC grading of muscle power differed by more than two grades between the corresponding muscles of the right and left extremity); (2) >10 mononuclear leukocytes in the spinal fluid; (3) conditions such as diabetic or alcohol neuropathy, neuropathies associated with industrial agents, metals and drugs, poliomyelitis, and porphyria; (4) electrodiagnostic study consistent with demyelination. All patients clinical features including age, sex, presence of preceding infections, vaccination, cranial nerve involvement,time to nadir, pattern of limb weakness, Hughes grade and clinical course were assessed. These patients were followed up monthly for six months. During the study period we found that the clinical presentation of AMAN showed certain distinctive features in comparison to AIDP which also presented to us in the same period. We then compared the clinical features of patients with AMAN and AIDP to detect any major differences in their clinical presentation.

ObservationsOur series had 12 cases of AMAN. During the same period there were 66 AIDP cases, four cases of Miller Fischer syndrome and two AMSAN; making a total of 84 cases

of GBS. Thus AMAN represents about 14% of GBS cases presenting to our department. The clinical features of AMAN patients are given in Table 1. There were eight males and four females. The mean age was 33.8 years (range 11-73). Only six patients had a preceding infection (three gastrointestinal and three respiratory). Nerve conduction data is given in Table 2. All AMAN patients except two had a characteristic pattern of distal upper extremity weakness i.e. severe finger extensor weakness in presence of relatively normal wrist extension, wrist flexion and finger flexion [Table 3]. Proximal upper extremity weakness (MRC Grade 3-4) was seen in 10 patients. Proximal (MRC Grade 2-4) as well as distal (MRC Grade2-4, Grade 2 power in only one patient) lower extremity weakness was seen in all patients. In the lower extremity Grade 2 weakness occurred proximally in only two patients who were nonambulant at presentation. Only one patient had bilateral facial palsy. One patient had hyperreflexia. One patient had hyporeflexia with extensor plantar response. None of these patients progressed to respiratory paralysis requiring ventilator support. All patients were ambulant at the two-month follow up but the finger extension weakness still persisted, albeit to a lesser degree in eight patients.

There were 55 AIDP patients for whom complete clinical and electrophysiologic data [Table 4] are available. There were 31 males and 24 females. A preceding illness was seen in 43.5%. In MRC grading of the muscle power none of these patients had a selective finger extensor weakness. Whenever finger extensor weakness occurred in AIDP patients it was always associated with equally severe weakness in the finger flexors and much greater weakness in the proximal muscles of the limb. Cranial nerve palsies were seen in 32 (58%) patients. Thirteen patients (22%) required ventilator support. Three patients died.

Discussion

GBS is an acute neurological illness, the course of which may vary from a self-limiting illness to an acute fulminating illness with a mortality of approximately

Table 1: Clinical features of patients with AMAN

Age Sex Preceding infection Cranial nerve palsy Hughes grade at nadir Time to nadir (Days)

17 M Y* N* 3 673 M N N 2 938 M Y N 2 450 F Y N 3 532 M N Y 1 233 M N N 2 428 M Y N 4 623 F N N 3 411 F N N 2 340 F Y N 3 538 M Y N 4 424 M N N 2 3

Y* - Yes, N* - N0

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George, et al.: Finger drop sign

Table 2: Electrophysiological parameters on motor nerve conduction study in AMAN patients

Nerve Mean distal latency (ms)

Mean CMAP amplitude

(mv)

Mean nerve conduction

velocity (m/s)

Median 3.44 (3.7 0.31) 3.2 (7.5 2.4) 55.6 (55.5 4.4)Ulnar 2.8 (2.7 0.5) 3.1 (6.9 2.06) 57 (59.4 5.33)

Common peroneal

4.4 (3.9 0.6) 2.1 (5.8 2.2) 48 (45.7 4.83)

Tibial 4.1 (3.8 0.70) 2.9 (7.1 3.2) 46 (47.2 3.86)

Normative data in our electrophysiology lab are given in brackets

Table 4: Motor nerve conduction study in patients with AIDP

Nerve Mean distal

latency (Ms)

Mean CMAP amplitude

(mv)

Mean velocity

(m/s)

Conduction block (%)

Median 5.1 6.7 41 20Ulnar 5.06 6.2 38.5 15Common peroneal

6.18 5.3 32.7 17

Tibial 5.9 5.8 33.6 -

Table 3: MRC grading (average) of muscle power in the different muscle groups in AMAN

Finger flexion

Finger extension

Wrist extension

Wrist flexion

Shoulder abduction

Hip flexion

Hip extension

Foot dorsiflexion

Foot plantar flexion

4 4 4 4 4 3 3 3 3

4 2 4 5 5 4 4 3 34 1 5 5 4 4 4 4 43 0 3 3 3 4 3 3 34 0 3 4 4 4 4 3+ 44 1 3 4 5 4 3 4 43 0 2 3 3 2 3 3 3

4 2 5 5 4 3 3 4 45 2 5 5 4 4 4 4 43 2 3 3 4 4 4 3 33 0 3 3 3 2 3 2 34 2 4 4 4 3 3 4 4

4-15% and permanent disability in about 20%. Patients with AMAN were considered to have greater long-term disability[9] whereas patients with AIDP were generally at high risk for rapid deterioration and need of mechanical ventilation.[10]

The previous studies have not stressed upon the clinical features of AMAN. In our small series we found that AMAN patients had a characteristic pattern of severe distal upper limb weakness with varying degrees of proximal weakness. This pattern consisted of severe finger extensor weakness (i.e. at the metacarpophalangeal and interphalangeal joints) in the presence of relatively normal power in finger flexion, wrist flexion and wrist extension-the finger drop sign [Figure 1]. This extensor weakness was not due to posterior interosseous nerve involvement alone, as to some extent lumbricals were also involved. But the key feature is the selectivity i.e. very weak finger extension and reasonably preserved finger flexion, wrist flexion and extension. This finger extensor weakness was bilateral in all the AMAN patients. It was the presenting symptom in four patients. None of our patients with AMAN had proximal muscle weakness in the absence of distal involvement. Proximal weakness was mild in comparison to the distal weakness, particularly in the upper extremity. Only two patients had severe proximal weakness rendering them non- ambulant. Finger extensor weakness exceeding MRC Grade 3

was present in 27(49%) patients with AIDP. But this weakness was never selective i.e. it affected both extensors and flexors equally and was always associated with severe proximal muscle weakness. It was neither the presenting symptom nor the dominant symptom. Thus predominant weakness of finger extensors seems to be relatively specific for the AMAN variant of GBS.

One of our patients had hyperreflexia. Though this doesnt satisfy the original clinical criteria where areflexia is a factor required for making the diagnosis, the clinical course was consistent with GBS and electrophysiology showed reduced amplitudes of the CMAP. One patient had hyporeflexia and extensor plantar response. This does not exclude GBS because in the article by Asbury[11] it was mentioned that some patients might show a variant pattern with extensor plantar response. So if the whole clinical picture fits GBS, the presence of a mere extensor plantar does not exclude the diagnosis. Deep tendon reflexes may be preserved throughout the disease course in patients with AMAN and have been considered indicators of rapid clinical recovery.[12,13] Moreover, 48% of Chinese and 33% of Japanese patients with AMAN showed hyperreflexia in the recovery phase.[14,15] In Europe, patients with pure motor GBS had preserved tendon reflexes up to MRC Grade 3 paresis, and more recently, an AMAN patient with hyperreflexia has been reported.[16] Many believe that the diagnostic criterion of areflexia should therefore be applied only to the sensory- motor forms of GBS.

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Fifty-eight per cent of patients with AIDP had cranial nerve palsy while only one patient with AMAN had cranial nerve palsy (8%). This paucity of cranial nerve involvement is another characteristic feature of AMAN. Viser et al.,[17] in their study on pure motor forms of GBS also observed the same.

All our AMAN patients improved and were ambulant independently at two months but the finger drop still persisted in eight of the 12, consistent with previous reports of long period to recovery in patients with axonopathy. There is controversy regarding the recovery patterns in patients with AMAN. Some studies have shown rapid clinical recovery whereas others have shown poor recovery with persistent disability. In those cases showing rapid clinical recovery authors postulate a distal conduction block at the motor nerve terminal as the pathologic basis for the low-amplitude CMAP and the rapid recovery due to reversal of conduction block at the motor nerve terminals following treatment.[18] Studies employing motor nerve terminal biopsy have proven this point. Those studies showing poor clinical recovery suggest a primary axonal degeneration as the basis for poor recovery. In a pathological study of three patients with AMAN Feasby et al.,[19] found evidence of axonal degeneration in the distal segments of the nerves as well as in the ventral roots and moderate axonal degeneration. McKhann et al.,[20] in their autopsy study on AMAN patients found non-inflammatory demyelination and predominant axonal degeneration in the ventral roots. Thus the pathological basis for the low CMAP and hence recovery is not uniform in AMAN.

AMAN was recognized as a distinct entity in the early nineties. McKhann reported a large series of 90 patients from China.[14] These patients with AMAN were largely children from rural areas. Bias towards children is due to the fact that this study was done in a childrens hospital in China. In this study he reported a rapidly evolving

weakness of proximal muscles and cranial nerve palsies. He did not highlight any distal involvement. But in that study 25 patients were followed up till one year in whom 17 patients (all ambulant) still had distal weakness with mild atrophy of the hands and feet. This suggests that these patients might have had severe distal weakness also at initial presentation which may have been overlooked because of equally severe or greater proximal weakness and cranial nerve palsies. A second large series of AMAN patients was reported by Visser et al., from the Dutch Guillain-Barr study group.17] In this series they found 14 patients as having a pure motor phenotype clinically. This group had certain specific features such as shorter time from onset to nadir, predominant distal weakness, lower incidence of cranial nerve palsies and less need for ventilatory support. But electrophysiologically their cases had evidence of distal demyelinating pathology suggesting that a distal conduction block could have caused the low amplitude of CMAPs. Our cases did not show any demyelinating features electrophysiologically. So electrophysiology-wise our cases have greater similarity to the series from China with normal distal latencies and markedly reduced CMAP amplitudes. But in that series there was dominant proximal weakness, the majority had cranial nerve palsies and many required ventilatory assistance suggesting a more fulminant entity whereas our clinical picture is milder. So our cases fall in the middle of this spectrum where the weakness is predominantly distal, cranial nerve palsies are few, course less fulminant and electrophysiology suggestive of pure motor axonopathy. These regional differences observed between the studies could be due to the different antibodies targeting different sites along the peripheral nervous system and causing variable degree of axonal damage or there could be some genetic factor which might influence the way one responds to an immunological insult and this might be different in different populations. Future studies may enhance our knowledge about this very interesting clinical entity and may offer newer therapeutic strategies.

Figure 1a: Marked weakness of finger extensors Figure 1b: Normal power in finger flexors

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Selectivity of weakness among different muscles or muscle groups has always fascinated the clinicians in arriving at specific diagnosis of motor system disease. Whether it is preferential involvement of anti-gravity muscles in upper motor neuron disorders, differential involvement of trunk (hypotonic) and limb (spastic) muscles in cerebral palsy or the affection of specific group of muscles in muscular dystrophies, these all are the examples of exploitation of selectivity of muscle involvement for the purpose of clinical diagnosis. Not much has been said in this regard about generalized neuropathies except predilection of some for proximal muscles and of majority for distal muscles. In this context the article Finger drop sign in Guillain Barre syndrome is a remarkable piece of work suggesting the diagnosis of AMAN variety of GB

Sunil Pradhan

Department of Neurology, Institute of Human Behaviour & Allied Sciences, Dilshad Garden, Delhi

Invited Commentary

syndrome as against AIDP variety whenever predominant weakness of finger extensors was encountered. With an exception of toxic neuropathy due to lead exposure, which in any case has a sub-acute or a chronic presentation, no acute generalized polyneuropathy is known to have such predilection for extensors of the fingers. With time and validation finger drop sign is likely to gain popularity among neurophysicians in the clinical diagnosis of AMAN. Though finger drop sign has been described in a variety of other neurological disorders, most of them are focal disorders leading to unilateral posterior interosseous nerve syndrome and are obviously out of context due to focal nature of these diseases. Among the more generalized disorders finger drop sign has been observed with multifocal motor neuropathy, motor

George, et al.: Finger drop sign

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Accepted on 25-04-09Source of Support: Nil, Conflict of Interest: None declared.

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